The major consequence of congestive heart failure (CHF) is the activation of the sympathetic nervous and renin-angiotensin systems. The resulting vasoconstriction and volume overload increase wall stress on the heart, which then increases the demand for oxygen by the myocardium. These changes lead to further activation of these systems, creating a vicious cycle that ultimately results in deterioration of the patient's health. Therapy traditionally has focused on symptom relief, not on the underlying events. The two types of agents currently used in the treatment of CHF are angiotensin-converting enzyme (ACE) inhibitors and the newer angiotensin-II antagonists. Both are effective but differ in mechanisms of action and reported side effects. Brunner-La Rocca and colleagues compared the properties of ACE inhibitors and angiotensin-II antagonists to identify major differences and provide a framework for additional study of these agents.

Several large studies have shown that ACE inhibitors significantly reduce morbidity and mortality in patients with CHF. However, these agents do not completely block the renin-angiotensin system, which may have some impact on their long-term effectiveness. ACE inhibitors are also associated with significant adverse effects, including hypotension, renal failure and a dry cough. Angiotensin-II antagonists recently have been introduced as treatment options, as they specifically block one portion of the renin-angiotensin system. In addition, their side effect profile is better than that of ACE inhibitors. Recent studies have found that both agents are equally effective in the treatment of CHF. However, until larger trials comparing the two agents are conducted, ACE inhibitors remain the initial treatment of choice. Combination therapy using both ACE inhibitors and angiotensin-II antagonists should improve outcomes, but there are no studies that support this therapy at the present time.

Although ACE inhibitors have proved effective in the treatment of CHF, only 30 to 50 percent of patients receive these medications. Tolerability may be one explanation, but the proportion of patients who cannot tolerate these agents is presently unknown. Most patients who are taking ACE inhibitors receive dosages lower than those given in large clinical trials, even though higher dosages are clearly superior in providing symptom relief, improving exercise performance and suppressing neurohumoral stimulation. Lack of knowledge about ACE inhibitors or concerns about safety and common adverse effects may also explain why these agents are under-prescribed or prescribed in low dosages. However, toleration of high dosages does not appear to be a problem in most patients.

The authors conclude that because angiotensin-II antagonists are still investigational, initial treatment of CHF should consist of therapy with ACE inhibitors, with emphasis on giving the higher dosages. The value of combination therapy still needs to be determined. In patients who cannot tolerate ACE inhibitors, angiotensin-II antagonists may be a good alternative. The challenge of management of CHF in the future will be to develop customized treatment for individual patients by selecting from a variety of drugs proved to be effective in the treatment of CHF and well tolerated by patients.

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